ST3GAL5通过激活PPAR和抑制PI3K/AKT途径抑制膀胱癌的恶性生物学行为  

ST3GAL5 inhibited malignant biological behavior of bladder cancer by activation of the PPAR pathway and inhibition of the PI3K/AKT pathway

作　　者：谭明辉 郝雨 倪钊[1] 李强[1] 王勤章[1] 欧阳松[1] Tan Minghui;Hao Yu;Ni Zhao;Li Qiang;Wang Qinzhang;Ouyang Song(Dept of Urology,The First Affiliated Hospital,School of Medicine,Shihezi University,Shihezi 832000)

机构地区：[1]石河子大学第一附属医院泌尿外科,石河子832000

出　　处：《安徽医科大学学报》2023年第9期1458-1466,共9页Acta Universitatis Medicinalis Anhui

基　　金：兵团科技攻关项目(编号:2018AB023);石河子大学第一附属医院博士科研资助基金(编号:BS202110)。

摘　　要：目的研究ST3β-半乳糖苷α-2,3-半乳糖基转移酶5(ST3GAL5)对膀胱尿路上皮癌(BLCA)生物学行为的影响和潜在机制。方法利用生物信息分析确定与膀胱癌相关的差异表达基因。然后筛选出合适的膀胱癌细胞系。体外实验通过细胞计数盒-8(CCK-8)、5-乙炔基-2′脱氧尿嘧啶核苷(EdU)、菌落形成实验、转孔迁移、流式细胞仪凋亡实验和划痕实验评估ST3GAL5对膀胱癌生物行为的影响。使用癌症基因组图谱(TCGA)数据库对ST3GAL5基因进行了京都基因和基因组百科全书(KEGG)、基因集富集分析(GSEA)。最后,使用Western-blot技术验证其增殖和转移的相关通路。结果生物信息学分析和实验测量的结合表明,ST3GAL5的表达在人类的BLCA细胞系中是异常下调的。通过癌症细胞系百科全书(CCLE)数据库,成功筛选出HT-1376细胞系进行体外实验。实验结果发现上调ST3GAL5后膀胱癌的恶性生物学行为被抑制。GSEA富集分析显示,ST3GAL5及其共表达的基因通过激活PPAR途径和抑制PI3K/AKT途径抑制了膀胱癌的细胞增殖、侵袭和转移。Western-blot实验结果验证了ST3GAL5在膀胱癌中过表达后,PPAR信号通路的关键蛋白出现了明显的增加,PI3K/AKT信号通路的关键蛋白出现了明显的减少(P<0.05)。结论ST3GAL5基因可能作为膀胱癌的致癌抑制基因,可能通过激活PPAR信号通路和抑制PI3K/AKT信号通路的相关分子来抑制膀胱癌细胞的增殖、侵袭和转移。Objective To the effects and potential mechanisms of ST3GAL5 on biological behaviors of Bladder Urothelial Carcinoma(BLCA).Methods Differentially expressed genes related to bladder cancer were identified using microarray analysis.Suitable bladder cancer cell lines were then screened.In vitro experimental measurements,including CCK8,EdU,colony formation assays,transwell migration,flow cytometry apoptosis experiments,scratch assay,were used to evaluate the effects of ST3GAL5 on biological behaviors of BLCA.ST3GAL5 gene Kyoto Encyclopedia of Genes and Genomes(KEGG),gene set enrichment analysis(GSEA)were analyzed using The Cancer Genome Atlas(TCGA)database.Finally,Western blot technology was used to verify the classical proliferation and metastasis related pathway factors.Results The combination of bioinformatics analyses and experimental measurements demonstrate that ST3GAL5 expression is aberrantly down-regulated in human cell lines of BLCA.Through Cancer Cell Line Encyclopedia(CCLE)database,HT-1376 cell lines were successfully screened for vitro test.Upregulation of ST3GAL5 was found to suppress the malignant biological behaviour of bladder cancer.GSEA enrichment analyses exhibited that ST3GAL5 and its co-expressed genes inhibited cell proliferation,invasion and metastasis of bladder urothelial carcinoma by activation of the PPAR pathway and inhibition of the PI3K/AKT pathway.The results of Western blot experiments verified that the key proteins of the PPAR signaling pathway showed a significant increase and the key proteins of the PI3K/AKT signaling pathway showed a significant decrease(P<0.05)after ST3GAL5 overexpression in bladder cancer.Conclusion ST3GAL5 gene might act as an oncogenic suppressor gene in bladder cancer,possibly inhibit the proliferation,invasion and metastasis of bladder cancer cells by activating the PPAR signaling pathway and inhibiting related molecules in the PI3K/AKT signaling pathway.

关 键 词：膀胱癌 ST3β-半乳糖苷α-2 3-半乳糖基转移酶5 癌症基因组图谱 高通量基因表达 癌症细胞系百科全书 蛋白质印迹 京都基因和基因组百科全书 

分 类 号：R737.14[医药卫生—肿瘤]